Alzheimer’s disease (AD) research is often limited by long experimental timelines and models that fail to capture the full spectrum of human pathology. Here we present FAD3T, a next-generation transgenic mouse model on the C57BL/6J background carrying humanized APP, PSEN1, and MAPT genes with familial AD mutations.
FAD3T mice display translational plasma biomarkers as early as 1 month, including Aβ40, Aβ42, p-tau181, p-tau217, and neurofilament light chain (NfL). The model recapitulates a progressive amyloid cascade, followed by phosphorylated tau pathology and neuroinflammation by 6 months. These pathological changes translate into early spatial memory deficits, emerging at 3 months in females and 4 months in males, reflecting clinically relevant sex differences.
Overall, FAD3T integrates early biomarker translatability, progressive AD pathology, and sex-specific phenotypes, providing a powerful platform to accelerate Alzheimer’s disease research and therapeutic development.